Doxazosin: A study in a cohort of patients with hypertension in general practice-An interim report The objective of this study was to assess the safety and efficacy of doxarosin in a substantial cohort of hypertensive patients drawn from general practice. A total of 4027 patients entered the study, 1472 of whom (36.6%) were untreated hypertensive patients. Patients were not advised to change diet, smoking habit, or life-style during the study. Twenty-one percent were cigarette smokers, and concurrent diabetes was present in 2.3%. Baseline blood cholesterol exceeded 200 mg/dl (5.2 mmol/L) in 90% and 250 mg/dl (6.5 mmol/L) in 56% of patients. The mean decrease in blood pressure produced by doxarosin was 22/15 mm Hg after 10 weeks of therapy; there was a mean decrease in heart rate of 1 beat/min. The mean maintenance dose for all patients was 3.1 mg/day. Side effects considered related or possibly related to treatment were reported in 705 patients. Treatment was discontinued in 233 patients (5.6%) because of adverse events related or possibly related to treatment with doxazosin. Doxarosin produced a significant (p < 0.001) decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and a significant increase in high-density lipoprotein cholesterol and the ratio of high-density lipoprotein:total cholesterol. The potential reduction in lo-year coronary heart disease risk (according to the Framingham equation) was calculated to be 20.4%. (AM HEART J 1991;121:266-73.)

Christopher

G. Langdon,

MB Maidenhead,

England

Doxazosin is a highly selective inhibitor of sympathetic stimulation of postsynaptic al-adrenoreceptors. Doxazosin produces a reduction in blood pressure by decreasing peripheral vascular resistance without causing reflex tachycardia.lm3 The plasma half-life of the drug is between 1g4 and 22 hours5 and does not appear to be influenced by age6, 7 or renal dysfunction.8 Thus a single daily dose of doxazosin is sufficient to control hypertension. Controlled double-blind studies have shown that doxazosin produces a significant reduction in standing and supine blood pressure, which is maintained throughout the 24-hour dosing interval.g Hypertension is only one of a number of risk factors implicated in coronary heart disease (CHD); elevated serum cholesterol, reduced high-density lipoprotein (HDL) cholesterol, smoking, and glucose intolerance increase the risk of CHD and often coexist in the hypertensive population to produce a more than additive effect on the risk of CHD.‘O-13 Doxazosin has a potentially favorable effect on the serum From

the Symons

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Medical

requests: Christopher Way, Maidenhead,

Centre. G. Langdon, MB, Symons Medical Berkshire SL6 4AB, England.

Centre,

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lipid profile and has been found to reduce total plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels and to increase the levels of HDL cholesterol and the HDL:total cholesterol ratio.14 This is in contrast to some other antihypertensive agents, in particular @blockers and diuretics, which can adversely affect serum lipids.15-l8 This study was designed to evaluate the safety and efficacy of doxazosin in a substantial cohort of hypertensive patients drawn from general practice. Selection criteria were sufficiently broad to ensure that patients were representative of those seen routinely by family practitioners. This article is an interim report of the principal results in 4027 patients. METHODS Study design. The study was an open, noncomparative, multicenter evaluation of doxazosin in patients with mild or moderate hypertension (sitting diastolic blood pressure [DBP] 95 to 114 mm Hg). Patients over 18 years of age, of either sex, and with untreated or inadequately controlled hypertension, gave informed consent to participate in the study. Patients already receiving antihypertensive treatment could discontinue this at or before trial entry or could

continue to take the therapy at a constant dose and administration schedule throughout the study. The fol-

Volume 12 1 Number 1, Part 2

UK general practice

lowing criteria excluded a patient from entering into the study: malignant or secondary hypertension, risk of pregnancy, pregnancy, lactation, cerebrovascular accident or acute myocardial infarction within the past 3 months, unstable angina pectoris, known significant hepatic, renal, endocrine, gastrointestinal, or hematologic disease, orthostatic hypotension, or a previous history of intolerance to a-inhibitors. Patients were not advised to change their diet, smoking habits, or life-style during the study. There was a 2-week observation period between screening and baseline, after which patients could receive doxazosin if they still met the selection criteria. Assessments were performed at screening, baseline, and after 2,4,6, and 10 weeks of treatment with doxazosin. Initially patients received 1 mg as a single daily dose, which could be increased by doubling to a maximum of 8 mg/day of doxazosin. The dose was increased at intervals of 2 weeks until DBP was

Doxazosin: a study in a cohort of patients with hypertension in general practice--an interim report.

The objective of this study was to assess the safety and efficacy of doxazosin in a substantial cohort of hypertensive patients drawn from general pra...
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